Aims: This project will further explore the epidemiology and genetic basis of Crohn's disease. The emphasis will be on the different subtypes or phenotypes of this disease to better understand the contribution of patient characteristics. Furthermore; based on this data, predictive models will be constructed for disease site and location as well as models for clinical course and severity. The focus will then be assessment of altered intestinal permeability in both patients and relatives as a potential marker for disease. METHODS: The study population will consist of 400 consecutive patients seen at the Meyerhoff Digestive Disease Inflammatory Bowel Disease Center at John Hopkins Hospital from February 1992- February 1996. These patients will be classified into distinct subtypes of Crohn's disease, based on anatomic site and level of transmural aggressiveness, through radiologic and histologic criteria. A questionnaire then will be developed, tested validated and applied to this population. A previously developed logistic regression model for site and type of disease based on family history will be applied to this population and then expanded to understand the importance of other characteristics on the development of a particular subtype. Furthermore, a new model will be constructed to understand the clinical course of a particular patient defined by need for surgery, dependence on immunosuppressives, and number of hospitalizations based on the individuals subtype and other unique characteristics. The goal will be to identify in the fixture patients who are more likely to have severe disease and target them for more aggressive early intervention. The project will then study the patients with quiescent small bowel disease and there first degree relatives to understand the prevalence and concordance altered intestinal permeability in families. This prevalence study will be performed after the ingestion of aspirin and lactulose and mannitol as permeability probes. A population of relatives will then be identified who may have subclinical disease or may be predisposed to development of Crohn's disease in the future.